Muscle fatigue has been studied for over a century. Despite considerable gains in knowledge of the peripheral mechanisms underlying fatigue, very little is known about how the brain, the control center of any neuromuscular operation, modulates the activity of the fatiguing muscle. Because the functional outcome of muscle fatigue is a decline in the ability to generate force, the brain must adjust its output to maintain the desired muscle force. When a constant submaximal load or force is sustained, the surface electromyographic signal (EMG) typically increases. It is possible, therefore, that the brain also increases its activity during a low-force fatigue process. This possibility has not been tested. When a maximal force is sustained the force and EMG decline in parallel. Whether the level of brain activation changes during a sustained maximal voluntary contraction (MVC) is unknown. It is also not clear how the sensory information from the fatiguing muscle influences activities of cortical motor areas. Aim 1 is to quantify the changes in brain activation during fatigue involving MVC. Aim 2 is to determine the effect of low-force fatigue on the adjustment of brain activity. Aim 3 is to determine the effects of sensory feedback from the fatiguing muscles on brain activity. Brain activation will be determined by functional magnetic resonance imaging (fMRI) and motor-activity related cortical potential (MRCP) derived from electroencephalographic recordings (EEG). Preliminary fMRI results showed that (1) despite the differences at the periphery between the low-force (constant force, increasing EMG) and high-force (decreasing force and EMG) fatigue, the change in brain activity was surprisingly similar: brain activity increased during both tasks; (2) many higher-order cortical fields increased in activation during the later stage of the fatigue tasks; and (3) the motor cortex contralateral to the fatiguing muscle "fatigued" and the ipsilateral motor cortex increased its activity substantially as fatigue set in. It is hypothesized that (1) during both fatigue tasks (MVC and low-force), the overall brain activation level will increase, but the changes among different cortical fields will vary; (2) the higher-order motor areas and motor cortex ipsilateral to the fatiguing muscles will increase in activation during the later stage of the tasks; and (3) after blocking the sensory information from the fatiguing muscle, the contralateral motor cortex activity will increase more than when the sensory information is not blocked. Surface EMG and force will be recorded simultaneously with the brain images and MRCP data while subjects perform the fatigue tasks. This will enable the Principal Investigator to examine the central (brain) and peripheral (muscle) systems concurrently. The intent is that knowledge gained from these studies will provide primary data concerning the central nervous system activation during muscle fatigue. This knowledge will contribute to our understanding of the neuromuscular mechanisms underlying muscle fatigue and will have relevance for neurology and rehabilitation medicine.